England opener Strauss, 29, will lead his country after Flintoff was told to rest for at least four weeks while he recovers from an ankle injury.
Five players uncapped at international level have been named in the squad including Tim Bresnan, Glen Chapple, James Dalrymple, Ed Joyce and Alex Loudon. A sixth, Alastair Cook, has yet to make his ODI debut.
Flintoff has had scans on his left ankle injury and it is hoped the problem will heal with rest, although he may be sidelined for some time.
Surgery is not being considered at this stage and the ECBs Chief Medical Officer, Dr Peter Gregory, said: "During the 3rd Test at Trent Bridge, Andrew Flintoff had scans on his painful left ankle.
"These revealed calcified deposits in the area at the back of the ankle from which a bone spur was removed in February 2005.
"We have taken advice from two leading ankle surgeons who both agree that these may not be contributing to Andrews symptoms and that surgery would cause more trauma and the potential for more scarring and further calcified deposits. Hence, our view is that surgery is very much the last resort."
Chairman of Selectors, David Graveney, admitted England's injury-hit squad face a difficult time against Sri Lanka in The NatWest Series and The NatWest Twenty20 international.
Graveney said: "This will be a tough test for the team. Our first choice captain is injured and his nominated replacement Andrew Flintoff is also unavailable through injury as are a number of senior players.
"Andrew Strauss will again deputise as captain. He did an excellent job captaining the team in difficult circumstances in India, securing our only win in the series and will bring his experience of leading Middlesex to the role.
"There are significant changes in personnel from the One-Day squad which toured India and this will be an exciting opportunity for the new players in the squad to make an impression.
"All the uncapped players have performed well for their Counties this season and will bring different qualities to the squad.
"The selection of Tim Bresnan and Glen Chapple in particular is designed to provide the captain and coach with more flexibility in the bowling attack both at the beginning and the end of an innings."
Graveney is confident Michael Vaughan is getting closer to a return to international action, but insisted he will not be rushed back.
He added: "Michael Vaughan is making good progress with his recovery and we will continue to monitor his situation closely.
"We do not want to take any unnecessary risks with Michael and will wait until he is fully match fit before considering him for selection."
Squad: Andrew Strauss (Middlesex), Ian Bell (Warwickshire), Tim Bresnan (Yorkshire), Glen Chapple (Lancashire), Paul Collingwood (Durham), Alastair Cook (Essex), James Dalrymple (Middlesex), Stephen Harmison (Durham), Geraint Jones (Kent), Ed Joyce (Middlesex), Alex Loudon (Warwickshire), Sajid Mahmood (Lancashire), Kevin Pietersen (Hampshire), Liam Plunkett (Durham), Marcus Trescothick (Somerset).